A principal feature of metastatic tumors is their invasiveness. Cells detaching from primary tumors must cross membrane barriers to reach secondary target sites. Our studies are focused upon an aspect of the invasive process; namely, the chemotactic responsiveness of tumor cells to certain chemical stimuli. Using a human melanoma cell line we have found that these cells migrate in response to a material in their conditioned media which has an Mr of about 70KD and does not appear to be identical to other known attractants. The material may have plasminogen activator activity. These melonoma cells also respond to the peptides F-Met-Leu-Phe and bombesin. Additionally, we have found that a highly metastatic murine melanoma cell line selected from a subline of cells is markedly more chemotactically responsive than a poorly metastatic line from the same subline.